scholarly journals Resistance to renal damage by chronic nitric oxide synthase inhibition in the Wistar-Furth rat

2006 ◽  
Vol 290 (1) ◽  
pp. R66-R72 ◽  
Author(s):  
Aaron Erdely ◽  
Gary Freshour ◽  
Chris Baylis
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Nitric Oxide Synthase ◽  
Renal Injury ◽  
High Dose ◽  
No Production ◽  
Sd Rat ◽  
Sd Rats ◽  
Oxide Synthase ◽  
The Impact

Chronic nitric oxide synthase inhibition (NOSI) causes chronic kidney disease (CKD) in the Sprague Dawley (SD) rat. We previously showed that the Wistar-Furth (WF) rats are resistant to several models of CKD and maintain renal nitric oxide (NO) production compared with SD rats, whereas low-dose NOSI caused progression of CKD in WF rats. Here, we evaluate the impact of high-dose chronic NOSI in WF and SD rats, as well as intrarenal responses to an acute pressor dose of NOSI in the normal WF. Rats were given NG-nitro-l-arginine methyl ester (l-NAME) (150 and 300 mg/l for 6–10 wk) in the drinking water after an initial bolus tail vein injection. Both strains showed significant reductions in total NO production with chronic l-NAME. SD given 150 mg/l l-NAME for 6 wk developed proteinuria and renal injury, whereas WF rats receiving 150 mg/l l-NAME for 6–10 wk or 300 mg/l for 6 wk developed no proteinuria and minimal renal injury. Blood pressure was significantly elevated with chronic NOSI in both strains but was higher in the SD rat. There was little impact on renal nitric oxide synthase expression with l-NAME, except that cortical endothelial nitric oxide synthase abundance increased in WF after 6 wk (150 mg/l). Micropuncture experiments with acute pressor NOSI resulted in similar increases in systemic blood pressure in SD and WF rats, whereas WF rats showed a much smaller increment in glomerular blood pressure compared with SD rats. In conclusion, WF rats do not develop renal injury after chronic NOSI at, or above, a dose that causes significant injury in the SD rat. This protection may be associated with protection from glomerular hypertension.

Blunted respiratory responses to hypoxia in mutant mice deficient in nitric oxide synthase-3

2000 ◽  
Vol 88 (4) ◽  
pp. 1496-1508 ◽  
Author(s):  
David D. Kline ◽  
Tianen Yang ◽  
Daniel R. D. Premkumar ◽  
Agnes J. Thomas ◽  
Nanduri R. Prabhakar
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Nitric Oxide Synthase ◽  
Blood Gases ◽  
Mutant Mice ◽  
No Production ◽  
Experimental Conditions ◽  
Arterial Blood ◽  
Oxide Synthase ◽  
Respiratory Responses

In the present study, the role of nitric oxide (NO) generated by endothelial nitric oxide synthase (NOS-3) in the control of respiration during hypoxia and hypercapnia was assessed using mutant mice deficient in NOS-3. Experiments were performed on awake and anesthetized mutant and wild-type (WT) control mice. Respiratory responses to 100, 21, and 12% O2and 3 and 5% CO2-balance O2were analyzed. In awake animals, respiration was monitored by body plethysmography along with O2consumption (V˙o2) and CO2production (V˙co2). In anesthetized, spontaneously breathing mice, integrated efferent phrenic nerve activity was monitored as an index of neural respiration along with arterial blood pressure and blood gases. Under both experimental conditions, WT mice responded with greater increases in respiration during 12% O2than mutant mice. Respiratory responses to hyperoxic hypercapnia were comparable between both groups of mice. Arterial blood gases, changes in blood pressure,V˙o2, andV˙co2during hypoxia were comparable between both groups of mice. Respiratory responses to cyanide and brief hyperoxia were attenuated in mutant compared with WT mice, indicating reduced peripheral chemoreceptor sensitivity. cGMP levels in the brain stem during 12% O2, taken as an index of NO production, were greater in mutant compared with WT mice. These observations demonstrate that NOS-3 mutant mice exhibit selective blunting of the respiratory responses to hypoxia but not to hypercapnia, which in part is due to reduced peripheral chemosensitivity. These results support the idea that NO generated by NOS-3 is an important physiological modulator of respiration during hypoxia.

Effect of Antioxidant Therapy on Nitric Oxide Synthase (NOS) Expression in Hypertensive Rats

Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 705-705
Author(s):  
Nosratola D Vaziri ◽  
Zhenmin Ni ◽  
Debra L Trnavsky-Hobbs ◽  
Fariba Oveisi
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Nitric Oxide Synthase ◽  
Inos Expression ◽  
Antioxidant Therapy ◽  
No Production ◽  
Hypertensive Rats ◽  
Negative Feedback Regulation ◽  
Arterial Blood ◽  
Oxide Synthase

P66 Earlier studies have demonstrated evidence for increased reactive oxygen species (ROS) and enhanced nitric oxide synthase (NOS) expression and NO production in spontaneously hypertensive rats (SHR). Given the negative feedback regulation of NOS by NO, we hypothesized that enhanced NO inactivation by ROS may contribute to compensatory upregulation of NOS in SHR. The present study was designed to test this hypothesis. Eight-week old male SHR were treated for three weeks with either a placebo or the potent antioxidant, lazaroid (des-methyltirilazad, 10 mg/kg/day by gastric gavage). A group of age-matched male Wistar Kyoto (WKY) rats served as controls. Tail arterial blood pressure and urinary excretion of NO metabolites (i.e. nitrate and nitrite, NO x ) were measured. In addition, immunodetectable NOS isotype proteins in the vascular, renal, cardiac and cerebral tissues were measured by Western blot. Compared to the WKY group, the placebo-treated SHR group showed a marked elevation of blood pressure (129±6 vs 198±8 mmHg, P<0.01), a significant increase in urinary NOx excretion (714±82 vs 1344±187 μmol/g creatinine, P<0.01) and a significant upregulation of eNOS (given as relative optical density) in the aorta (27±3 vs 165±15*), kidney (99±3 vs 180±8*) and heart (17±4 vs 126±2*). Likewise, inducible NOS (iNOS) expression was increased in the aorta (27±3 vs 163±15*), kidney (7±3 vs 322±57*)and heart (30±1 vs 80±2*) of the untreated SHR when compared to the WKY controls. In addition, nNOS expression was elevated in the brain (10±1 vs 18±1*) and kidney (12±1 vs 20±2*) of the untreated SHR group. Lazaroid therapy ameliorated HTN (144±4 mmHg, P<0.01, vs untreated SHR group) and mitigated upregulation of eNOS in the aorta (85±13*), kidney (129±8*) and heart (59±10*). Similarly, antioxidant therapy lowered iNOS expression in the aorta (85±13*), kidney (99±15*) and heart (41±3*) of the treated SHR. However, it had no significant effect on renal and brain nNOS expressions (18±2 and 16±2, respectively). These findings support the role of oxidative stress in the genesis and/or maintenance of HTN and compensatory up-regulations of eNOS and iNOS expressions in SHR. *P<0.05

Selective neuronal nitric oxide synthase inhibition blocks furosemide-stimulated renin secretion in vivo

1995 ◽  
Vol 269 (1) ◽  
pp. F134-F139 ◽  
Author(s):  
W. H. Beierwaltes
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Nitric Oxide Synthase ◽  
Perfusion Pressure ◽  
Renal Perfusion ◽  
Macula Densa ◽  
Renin Secretion ◽  
Renal Perfusion Pressure ◽  
Neuronal Nos ◽  
Oxide Synthase

The macula densa is a regulatory site for renin. It contains exclusively the neuronal isoform of nitric oxide synthase (NOS), suggesting NO could stimulate renin secretion through the macula densa pathway. To test whether neuronal NOS mediates renin secretion, renin was stimulated by either the renal baroreceptor or the diuretic furosemide (acting through the macula densa pathway). Renin secretion rate (RSR) was measured in 12 Inactin-anesthetized rats at normal (104 +/- 3 mmHg) and reduced renal perfusion pressure (65 +/- 1 mmHg), before and after selective blockade of the neuronal NOS with 7-nitroindazole (7-NI, 50 mg/kg ip). 7-NI had no effect on basal blood pressure (102 +/- 2 mmHg) or renal blood flow (RBF). Decreasing renal perfusion pressure doubled RSR from 11.8 +/- 3.3 to 22.9 +/- 5.7 ng ANG I.h-1.min-1 (P < 0.01) (ANG I is angiotensin I). Similarly, in 7-NI-treated rats, reduced perfusion doubled RSR from 8.5 +/- 1.8 to 20.5 +/- 6.2 ng ANG I.h-1.min-1 (P < 0.01). Renal hemodynamics and RSR were measured in response to 5 mg/kg iv furosemide in 12 control rats and 11 rats treated with 7-NI. Blocking neuronal NOS did not alter blood pressure (102 +/- 2 mmHg), RBF (5.8 +/- 0.4 ml.min-1.g kidney wt-1), or renal vascular resistance (18.7 +/- 1.4 mmHg.ml-1.min.g kidney wt).(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Protein kinase Cδ regulates endothelial nitric oxide synthase expression via Akt activation and nitric oxide generation

2008 ◽  
Vol 294 (3) ◽  
pp. L582-L591 ◽  
Author(s):  
Neetu Sud ◽  
Stephen Wedgwood ◽  
Stephen M. Black
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Endothelial Nitric Oxide Synthase ◽  
Promoter Activity ◽  
Dominant Negative ◽  
No Production ◽  
Enos Expression ◽  
Akt Activation ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

In this study, we explore the roles of the delta isoform of PKC (PKCδ) in the regulation of endothelial nitric oxide synthase (eNOS) activity in pulmonary arterial endothelial cells isolated from fetal lambs (FPAECs). Pharmacological inhibition of PKCδ with either rottlerin or with the peptide, δV1-1, acutely attenuated NO production, and this was associated with a decrease in phosphorylation of eNOS at Ser1177 (S1177). The chronic effects of PKCδ inhibition using either rottlerin or the overexpression of a dominant negative PKCδ mutant included the downregulation of eNOS gene expression that was manifested by a decrease in both eNOS promoter activity and protein expression after 24 h of treatment. We also found that PKCδ inhibition blunted Akt activation as observed by a reduction in phosphorylated Akt at position Ser473. Thus, we conclude that PKCδ is actively involved in the activation of Akt. To determine the effect of Akt on eNOS signaling, we overexpressed a dominant negative mutant of Akt and determined its effect of NO generation, eNOS expression, and phosphorylation of eNOS at S1177. Our results demonstrated that Akt inhibition was associated with decreased NO production that correlated with reduced phosphorylation of eNOS at S1177, and decreased eNOS promoter activity. We next evaluated the effect of endogenously produced NO on eNOS expression by incubating FPAECs with the eNOS inhibitor 2-ethyl-2-thiopseudourea (ETU). ETU significantly inhibited NO production, eNOS promoter activity, and eNOS protein levels. Together, our data indicate involvement of PKCδ-mediated Akt activation and NO generation in maintaining eNOS expression.

Effect of magnesium supplementation on blood pressure and vascular reactivity in nitric oxide synthase inhibition-induced hypertension model

2015 ◽  
Vol 37 (8) ◽  
pp. 633-642 ◽  
Author(s):  
Filiz Basralı ◽  
Günnur Koçer ◽  
Pınar Ülker Karadamar ◽  
Seher Nasırcılar Ülker ◽  
Leyla Satı ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Nitric Oxide Synthase ◽  
Vascular Reactivity ◽  
Magnesium Supplementation ◽  
Induced Hypertension ◽  
Oxide Synthase
Sign in / Sign up

Export Citation Format

Share Document